Production of high purity radioactive indium-113m



United States Patent 3,450,597 PRODUCTION OF HIGH PURITY RADIOACTIVEINDIUM-113m Henry H. Kramer, Mahwah, N.J., and Hirofumi Arino, Sufiern,N.Y., assignors to Union Carbide Corporation, a corporation of New YorkNo Drawing. Filed Dec. 23, 1966, Ser. No. 604,152

Int. Cl. G21g 1/02 U.S. Cl. 176-16 9 Claims ABSTRACT OF THE DISCLOSURE Aprocess for producing radioactive indium-113m by eluting from neutronirradiated tin that is retained on a silica gel substrate.

This invention relates to a novel process for the production ofradioactive indium-113m. In one aspect, this invention relates to anovel process for the production of radioactive indium-113m in highyields. A further aspect of this invention is directed to a novelprocess for the production of radioactive indium-113 which can beobtained in a high degree of purity.

Recent medical investigation has shown that indiumll3m is an extremelyuseful tool for diagnosis. High purity indium-113m is used primarily asa radioisotope in a variety of medical research and diagnosis. It iswell suited for liver, lung, blood pool and tumor scanning, and ispreferred over other radioactive isotopes because of its short half-lifewhich results in reduced exposure of the organs to radiation. Inaddition to medical uses, indium- 113m can also be employed inindustrial applications, such as in the measurement of flow rates,process control, radiometric chemistry, and the like. Since theradioisotope sought to be used has such a short half-life, it is commonpractice to ship the users of the isotope the parent element; in thiscase neutron irradiated tin. The user then extracts the indium-113m fromthe tin as his needs require. The production of indium-113m and itsdecay is illustrated as follows:

811 (n, 'y) Sn" In In (Stable) where 113 is obtained by neutronirradiation of 112 113 decays by the electron capture process to 113mwith the half-life of 118 days; 113m a metastable isotope, decays to theground state, 113 by the isomeric transition process with the half-lifeof 104 minutes.

In the past, radioactive indium-113m has been produced by a variety ofmethods. For example, I. Stonski and V. N. Pybakov (Chemia Analityczna,4, 877, 1959) prepared an indium-113m generator using an anion exchangeresin. The indium-113m was eluted with 3 molar hydrochloric acid. Theradiochemical purity of indium-113m was approximately 99 percent. Theindium-113m solution thus obtained was not suitable for medicalformulation because of the strong acid strength, the significant tin-113breakthrough and the possible contamination by the radiation degradationproducts of the organic resin. Another type of generator developed inthe Oak Ridge National Laboratory used hydrous zirconium oxide as theadsorber of tin-113 from which indium-113m was eluted with methyl ethylketone.

However, to date, none of the work reported in literature has beenentirely successful in the development of an indium-113m generator whichmeets present day medical requirements. It is therefore an object ofthis invention to provide a more eflicient method for producingradioactive indium-113m. Another object of this invention is to providea process for preparing radioactive indium in a high degree of purityand by an extremely reproducible process. A further object of thisinvention is to provide a process which avoids the need for separatingradioactive products and other impurities. These and other objects willreadily become apparent to those skilled in the art in the light of theteachings herein set forth.

It has now been discovered that the aforementioned objects can beachieved by a process which comprises the steps of (a) irradiating a tincompound, (b) dissolving the tin compound, (c) diluting the dissolvedtin compound with water, (d) contacting the diluted tin solution withsilica gel, (e) selectively extracting indium-113m from the silica gelsubstrate with dilute acid.

Operating in the aforesaid manner provides a selective separation ofindium-113m from all other elements in the dissolved tin compound withvery high efficiency, i.e., over percent. In addition the process ofthis invention is readily reproducible and simple to operate.

Although a variety of tin compounds are suitable for use in the processof this invention the preferred tin target is thin metal. Particularlypreferred is tin metal enriched in the stable tin-112 isotope. In theevent that tin compounds other than tin metal are employed, it ispreferred to isolate the tin component after irradiation. Illustrativetin compounds which can be employed as the source of tin include, amongothers, tin metal, tin oxide, tin nitrate, tin sulfate, organic tincompounds such as tetraphenyl tin, and the like.

Irradiation of the tin compound by neutrons is a Well known techniqueand can be effected by placing the tin compound in the irradiation zoneof a nuclear reactor, neutron generator, or neutron isotopic source.

Thereafter, the irradiated tin compound is dissolved in a suitablesolvent. In the case of tin metal, concentrated hydrochloric acid isemployed. For other tin compounds it may be necessary to employ a basicsolvent such as sodium hydroxide and perform additional reactions toisolate the tin.

It has been found to be advantageous to dissolve the tin metal inhydrochloric acid in the presence of an oxidizing agent to aid in thedissolution and to insure that the tin is in the stannic (+4) oxidationstate. Hydrogen is preferred inasmuch as it is easily removed from thetin solution by heating. Other oxidants such as bromine water,permanganate, and the like, can be used but are less preferred.

Thereafter the dissolved tin compound is diluted with water in thepresence of a drop or two of bromine water to insure the properoxidation state (+4) of the tin. The solution is adjusted to provide atin concentration in 0.3 to 0.5 molar HCl of at least about 0.5milligram of tin, as the element, per milliliter of solution.

Silica gel is then immediately contacted with the dilute acid solutioncontaining the tin. The preferred mesh is from 20to 200. The silica gelcan be added to a vessel containing the tin solution until thoroughlywet and then heated to enhance the deposition of the tin on the gel.Preferably the solution is heated to about 40 to C. and more preferably80 C. from 15 to 20 minutes followed by digestion at room temperaturesfor not less than about two hours.

Alternatively, the solution can be left at room temperature for a longperiod of time. However, the amount of tin deposited has been shown notto be reproducible, and may take as long as several weeks.

The silica gel containing the tin is then transferred to an appropriateelution system such as a column, preferably glass, or other inertmaterial. The supernatant liquid is allowed to drain and the substratewashed with approximately 10 to 200- milliliters of 0.01 to 0.1 molarHCl, more preferably 0.07 molar HCl.

it has been observed that best results are obtained when' the column iseluted with 4 to 20 milliliter portions of 0.03 to 0.1 molar HClsolution. This is done by passing the desired volume of HCl through thecolumn and collecting the efliuent.

Numerous variations of the preferred embodiment described above may bepracticed, as will be apparent to those skilled in the art, withoutdeparting from the basic concepts of the present invention.

As previously indicated, the process of the present invention provides asimple, method for the preparation of indium-113m in a high degree ofefficiency. By this process recovery of indium-113m can be effected withhydrochloric acid in efliciencies of 90% and higher, over a pH range ofabout 0.5 to about 1.7 without appreciable dissolution of the silica gelor removal of any tin from the silica gel substrate.

A further advantage characteristic of the process of this invention, isthat the substrate and/or the entire elution system can be sterilized,i.e., by autoclaving at the normally prescribed temperatures andpressures.

In contrast, the previously known hydrous zirconium oxide, which canalso be loaded by the above-described procedure, has elutionefliciencies greater than 50 percent and normally less than 75 percentwhen eluted with hydrochloric acid over a pH range of about 1.4 to about1.6. A lower pH than 1.4 would result in appreciable dissolution of thezirconium oxide, while a higher pH results in decreased efliciencies.Under optimum elution conditions of both substrates, the majoradvantages of the present process are (a) higher efliciency of recoveryof indium-113m from the substrate, (b) greater operating pH range overwhich elficient elution can be effected, and (c) sterilization of thesubstrate by normal autoclaving methods, i.e., steam and pressure, onlyslightly reduces the recoverable indium-113m, for example about 5percent for the silica gel substrate as compared to about 20 to about 30percent for the zirconium oxide substrate.

The following example is illustrative:

Example I Tin metal (500 milligram) enriched in tin 112 is encapsulatedin high purity quartz tubing which is then in turn secondarilyencapsulated in aluminum tubing. The container is then placed in anuclear reactor neutron irradiation zone of a high thermal neutron flux.The capsule was irradiated for approximately 500 to 5000 hours. Thecontainer is removed from the radiation zone to an appropriate shieldedfacility. The tin is removed from its encapsulation material, dissolvedin concentrated HCl which contains several drops of hydrogen peroxide(30 percent) thereafter, the concentration was adjusted to milligrams oftin per 1 milliliter of 4 molar HCl. Prior to loading, the abovesolution was diluted 10:1 with water containing a few drops of brominewater. Approximately 20 milligrams of tin (20 milliliters of the dilutedsolution) is loaded on 5 milliliters wet volume of silica gel(approximately 4 grams) by contacting the silica gel with the solutionfor to minutes at 80 C. followed by 2 to 24 hours at room temperature.The silica gel solution is then loaded to a glass column 1 x 5centimeters which is shielded with an appropriate lead container. Thesupernate is permitted to drain and the silica gel washed with 125milliliters of 0.07 molar HCl. After an appropriate time period topermit the decay of the retained tin-113 to indium-113m the availableindium-113m on the column is removed by the addition of 5 milliliters of0.07 molar HCl.

4 Radiometric analysis of the eluted "indium-113m indicates that itcontains percent of the available indium- 113m and the radionuclidicpurity is greater than 99.98 percent. The total metal element impurityis less than 1 part per million as determined by emission spectroscopytechniques.

The substrate and/or the entire elution system can be sterilized byacceptable autoclave techniques with no reduction in radionuclidicimpurity, no increase in the metal element impurities and only a slightreduction in the amount of indium-113m recoverable.

Although the invention has been illustrated by the preceding example, itis not to be construed as being limited to the materials employedtherein, but rather, the invention encompasses the generic area ashereinbefore disclosed. Various modifications and embodiments of thisinvention can be made without departing from the spirit and scopethereof.

What is claimed is:

1. A :process for producing radioactive indium-113m which comprises thesteps of:

(a) irradiating a tin containing material in a neutron flux until thedesired amount of tin-113 is formed;

(b) dissolving the irradiated tin containing material containing theradioactive tin-113, to obtain a tin solution;

(c) diluting the tin solution with water;

(d) contacting silica gel with said dilute tin solution, heating to atemperature of from about 40 to about C., thereby loading the tin onsaid silica gel to provide an elution system, and

(e) selectively extracting said elution system with a solutionconsisting essentially of a dilute inorganic acid at a pH range of fromabout 0.5 to about 1.7 to separate indium-113 from its radioactiveparent tin-113 that is deposited on the silica gel.

2. The process of claim 1 wherein said tin containing material is tinmetal.

3. The process of claim 1 wherein said tin containing material is tinmetal enriched in the stable tin-112 isotope.

4. The process of claim 1 wherein said irradiated tin containingmaterial is dissolved in concentrated hydrochloric acid in the presenceof an oxidizing agent.

5. The process of claim 1 wherein said tin solution is diluted to aminimum tin concentration of at least 0.5 milligram per milliliter of0.3 to 0.5 molar hydrochloric acid.

6. The process of claim 1 wherein said diluted tin solution is contactedwith said silica gel and heated at a temperature of from about 40 to 100C., and then allowed to stand at room temperature.

7. The process of claim 1 wherein indium-1 13111. is selectivelyextracted with hydrochloric acid of a concentration of from about 0.01to 0.1 molar.

8. The process of claim 1 wherein said elution system is sterilized.

9. The process of claim 8 wherein said sterile elution system isextracted with sterile hydrocholric acid to provide a sterile solutioncontaining irradiated indium-113m.

No references cited.

BENJAMIN R. PADGETT, Primary Examiner.

H. E. BEHREND, Assistant Examiner.

U.S. Cl. X.R.

